Jenkins B G, Rosas H D, Chen Y C, Makabe T, Myers R, MacDonald M, Rosen B R, Beal M F, Koroshetz W J
Department of Radiology, MGH-NMR Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, USA.
Neurology. 1998 May;50(5):1357-65. doi: 10.1212/wnl.50.5.1357.
Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized 1H spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 HD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects.
亨廷顿舞蹈病（HD）是4号染色体上一个基因中（CAG）重复序列扩增的结果。该基因缺陷的一个后果可能是能量代谢的进行性损害。我们之前利用局部1H光谱法显示HD患者枕叶皮质乳酸增加。我们现在扩展了这些研究，结果显示，与17名正常对照者相比，31名HD患者枕叶皮质乳酸升高了近三倍（p < 10^(-11)）。三名症状前基因阳性患者的光谱在皮质区域与正常对照者相同，但八名中有三名在纹状体中显示乳酸升高。与最近报道的优势半球纹状体任务相关激活增加类似，我们发现HD患者纹状体乳酸水平明显不对称（左侧更高）。神经元变性的标志物，即N-乙酰天门冬氨酸（NAA）/肌酸降低和胆碱/肌酸水平升高，是对称的。纹状体中NAA降低和乳酸升高均与症状持续时间显著相关。当按年龄划分时，发现个体纹状体NAA丢失和乳酸增加与受试者的CAG重复次数直接相关，相关系数分别为0.8和0.7。在死后细胞丢失以及年龄与CAG重复长度之间也观察到类似的相关性。总之，这些数据为HD中神经元激活与能量代谢缺陷之间的相互作用提供了进一步证据，这种相互作用可能延伸至症状前个体。
